The Mechanism of Novel Potential Porphyrin Photosensitizer Mediated Phototherapy in SH-SY5Y Cell Lines and the Effect of TMeQ[6] Self-Assembly in Therapy

Porphyrin PSs, possessing high photosensitivity and stability, have widespread use in phototherapy. Furthermore, the use of Q[n]s as a carrier for PSs has contributed to enhancing the efficacy of photodynamic therapy. In the present study, we synthesized 2TMeQ[6]-TPPPA self-assembled compounds, comprising TMeQ[6] and 5, 10, 15, 20-tetra (4-pyridyl, N-propyl ammonia) porphyrin derivatives (TPPPA) (in a 2:1 ratio), to investigate their capacity to generate reactive oxygen species (ROS) and their effect of self-assembly with TMeQ[6] on the efficacy of human neuroblastoma cell line (SH-SY5Y). Our results demonstrate that both TPPPA and 2TMeQ[6]-TPPPA generate substantial amounts of ROS under laser irradiation, which is directly proportional to the duration of illumination. Furthermore, both compounds exhibited significant cytotoxic effects on SH-SY5Y cells, as demonstrated by the MTT assay. Western blotting revealed a marked increase in the expression of Cleaved caspase-3, Cleaved caspase-9, and Bax, and a decrease in the expression of Bcl-2, confirming that caspase-dependent apoptosis is involved in SH-SY5Y cell death induced by TPPPA photodynamic therapy. ROS overproduction plays a crucial role in this process, and NAC preconditioning was shown to reduce cytotoxicity and inhibit pro-apoptotic protein molecules. However, 2TMeQ[6]-TPPPA was less effective than TPPPA in terms of ROS production capacity and toxicity to SH-SY5Y cells after self-assembling with TMeQ[6]. In conclusion, our study explored that TPPPA can induce ROS overproduction leading to apoptosis, and its mediated photodynamic therapy is a highly effective treatment option for SH-SY5Y cells. After self-assembling with TMeQ[6], TPPPA retains its apoptotic pathway-inducing characteristics and acts as a carrier, but this is not conducive to the photodynamic enhancement of TPPPA.